Distinguishable DNA methylation defines a cardiac-specific epigenetic clock.

BACKGROUND: The present study investigates whether epigenetic differences emerge in the heart of patients undergoing cardiac surgery for an aortic valvular replacement (AVR) or coronary artery bypass graft (CABG). An algorithm is also established to determine how the pathophysiological condition might influence the human biological cardiac age. RESULTS: Blood samples and cardiac auricles were collected from patients who underwent cardiac procedures: 94 AVR and 289 CABG. The CpGs from three independent blood-derived biological clocks were selected to design a new blood- and the first cardiac-specific clocks. Specifically, 31 CpGs from six age-related genes, ELOVL2, EDARADD, ITGA2B, ASPA, PDE4C, and FHL2, were used to construct the tissue-tailored clocks. The best-fitting variables were combined to define new cardiac- and blood-tailored clocks validated through neural network analysis and elastic regression. In addition, telomere length (TL) was measured by qPCR. These new methods revealed a similarity between chronological and biological age in the blood and heart; the average TL was significantly higher in the heart than in the blood. In addition, the cardiac clock discriminated well between AVR and CABG and was sensitive to cardiovascular risk factors such as obesity and smoking. Moreover, the cardiac-specific clock identified an AVR patient's subgroup whose accelerated bioage correlated with the altered ventricular parameters, including left ventricular diastolic and systolic volume. CONCLUSION: This study reports on applying a method to evaluate the cardiac biological age revealing epigenetic features that separate subgroups of AVR and CABG.

Migraine with aura with onset in childhood and adolescence: long-term natural history and prognostic factors.

The long-term course of migraine with aura (MA) has been poorly explored. The present 11-year follow-up study assessed the long-term natural history and possible prognostic factors of MA with onset in childhood or adolescence. Patients were recruited from the original case records of our department, which are specifically designed to report all headache characteristics, aura symptoms and electroencephalogram (EEG) findings. A total of 77 patients (47 females; 30 males) whose records contained detailed descriptions of both headache and aura symptoms apparently meeting the International Classification of Headache Disorders (ICHD)-II criteria for MA (i.e., 1.2.1, 1.2.2, 1.2.6) underwent structured face-to-face follow-up headache interviews, all of which were conducted by the same neurologist, who has particular expertise in this field. A multivariate model (logistic regression analysis) was used to investigate the association between possible prognostic factors and the remission of both aura and headache at follow-up. The results of our study showed that 23.4% of the MA patients were headache-free at follow-up, 44.1% still had MA and 32.5% had a transformed headache diagnosis (i.e., fulfilling the criteria for ICHD-II 1.1. or 2). Patients with basilar-type migraine (1.2.6) showed the highest headache remission rate (38.5%). Our study seems to show that migraine with typical aura (1.2.1-1.2.2) is associated with a favourable evolution of aura symptoms over time (remission of aura in 54.1% of patients). Subjects experiencing only visual aura had a lower remission rate compared with those with visual +/- sensory +/- aphasic aura symptoms (36.8% vs. 61.5%, p = 0.054). A short headache duration (<12 hrs) and the presence of EEG abnormalities at baseline were the only significant predictors of aura remission at follow-up (odds ratio [OR] = 9.12, 95% confidence interval [CI]: 1.79 +/- 46.51, and OR = 4.76, 95% CI: 1.18 +/- 19.15, respectively). No significant predictors of headache remission were found. In conclusion, our results suggest that MA shows a favourable course. Further prospective studies with detailed EEG analysis both at baseline and at follow-up are needed in order to confirm the possible prognostic role of EEG abnormalities in MA. That said, it would, in our opinion, be highly premature at present to submit children with MA to EEG examinations for prognostication purposes.

Different patterns of movement-related cortical oscillations in patients with myoclonus and in patients with spinocerebellar ataxia.

OBJECTIVE: To assess whether different patterns of EEG rhythms during a Go/No-go motor task characterize patients with cortical myoclonus (EPM1) or with spinocerebellar ataxia (SCA). METHODS: We analyzed event-related desynchronization (ERD) and synchronization (ERS) in the alpha and beta-bands during visually cued Go/No-go task in 22 patients (11 with EPM1, 11 with SCA) and 11 controls. RESULTS: In the Go condition, the only significant difference was a reduced contralateral beta-ERS in the EPM1 patients compared with controls; in the No-go condition, the EPM1 patients showed prolonged alpha-ERD in comparison with both controls and SCA patients, and reduced or delayed alpha- and beta-ERS in comparison with controls. In both conditions, the SCA patients, unlike EPM1 patients and controls, showed minimal or absent lateralization of alpha- and beta-ERD. CONCLUSIONS: EPM1 patients showed abnormal ERD/ERS dynamics, whereas SCA patients mainly showed defective ERD lateralization. SIGNIFICANCE: A different behavior of ERS/ERD distinguished the two patient groups: the pattern observed in EPM1 suggests a prominent defect of inhibition occurring in motor cortex contralateral to activated segment, whereas the pattern observed in SCA suggested a defective lateralization attributable to the damage of cerebello-cortical network, which is instead marginal in patients with cortical myoclonus.

Implementation of the homeless families program: 2. Characteristics, strengths, and needs of participant families.

The characteristics and needs of homeless families participating in a large-scale services-enriched housing program are examined. Although not a representative sample, participants constitute one of the largest subsets of homeless families in the literature. Moreover, the sample, which encompasses nine sites, is focused on families with multiple problems who have been recurrently homeless. Differing constellations of needs and implications for service delivery are explored.

[Can alpha-interferon exacerbate a case of mixed cryoglobulinemia?]. / Può l'alfa interferone esacerbare una crioglobulinemia mista tipo II latente?

We describe a case of exacerbated mixed cryoglobulinemia in a patient previously treated with alpha-interferon, for chronic active hepatitis. The possible pathogenesis of this exacerbated mixed cryoglobulinemia and the relationship between cytokines, hepatitis viral infections and immune reactions is discussed.

The effectiveness of hospitalization in the treatment of paediatric idiopathic headache patients.

BACKGROUND: Headache is a disease that has a high social impact in the paediatric as well as in the adult population, often resulting in a significant reduction in the young patient's quality of life, reflected primarily in a greater number of days off school and increasingly frequent recourse to symptomatic drugs. The idea for this study came from the clinical impression that some paediatric headache patients might benefit more from inpatient than outpatient care. AIM: The aim of our study was to compare the effectiveness of hospitalization to outpatient care of patients with newly diagnosed frequent and disabling headache. METHODS: A pragmatic randomized open-label trial was conducted at the Child Neurology Clinic of the University of Pavia, Italy. Children and adolescents with a 2- to 6-month moderate-to-severe migraine or tension-type headache history were randomized to hospital admission or outpatient assessment and followed for 6 months. The efficacy of the two therapeutic strategies was measured by counting the number of responders in each arm. Other end points included the mean frequency and duration of attacks, the number of drug prescriptions taken to control pain, and the number of patients and physicians expressing satisfaction with treatment. RESULTS: The study population included 27 girls and 23 boys aged 8 through 18 years with migraine (23 cases) or tension-type headache (27 cases). Compared to outpatient assessment, hospital admission was correlated to a significant increase in the number of responders: 0 vs. 44% (1 month), 0 vs. 68% (3 months), and 12 vs. 68% (6 months). The mean frequency and duration of attacks were significantly lower in hospitalized patients (p < 0.0001). Hospitalization was correlated with a significant reduction of patients with severe headache (p < 0.005), a reduction of drug use, and a higher number of satisfied patients and physicians (p < 0.05). Logistic regression analysis confirmed the higher responder rate among hospitalized patients after adjusting for age, sex, diagnosis, and headache characteristics or admission. CONCLUSIONS: We think hospitalization reduces the emotional mechanisms that provoke stress in children and often induce or favour headache attacks. If these mechanisms can be interrupted, the management of disease may become easier and with enduring benefits.

Gastrospirillum Hominis associated chronic active gastritis: the first report from Italy.

Recently a spiral bacterium different from Helicobacter Pylori (HP) was observed in the human stomach and the name of Gastrospirillum Hominis (GH) was proposed for this organism. GH presence is reported to be not associated to HP but related to chronic active gastritis. We describe the case of a 31 year old male suffering from upper abdominal symptoms, who underwent oesophagogastroduodenoscopy, which revealed a picture of duodenal hyperemia. Gastric body showed a normal mucosa and absence of HP, while active chronic gastritis associated with HP was found in the antrum. In addition few spiral bacteria showing 4-5 spirals, larger than HP were observed within the gastric crypts and beneath the mucus layer in this site. This case represents the first report from our geographic area (Southern Italy) of the possibility of finding bacteria different from HP in the human stomach. The simultaneous HP presence does not allow us to relate the chronic active gastritis of the patient with the GH like bacteria. Our finding, however, suggests the possibility that HP and GH may be simultaneously present in the course of type B antral chronic inflammation. This association was not observed in previous investigations.

Are vascular disorders more prevalent in the relatives of children and adolescents with migraine?

The objective of the study was to assess whether a family history of vascular disorders is more common in children and adolescents with migraine than in the general population. Family history of stroke, arterial hypertension, myocardial infarction and diabetes was investigated by history taking in relatives of ambulatory children and young adults with migraine and in a control group. The odds ratios (ORs) with 95% confidence intervals (95% CI) were used as a risk measure. Using univariate and multivariate (logistic regression) analysis, family history was assessed in the whole sample and in subgroups by sex and age, degree of relationship (parents and grandparents vs. relatives), disease type (migraine with and without aura), and type of vascular disorder. The sample included 143 cases (migraine with aura 35, migraine without aura 108) and 164 controls aged 3-24 years (mean 12 +/- 3.8 years). Patients with migraine were at increased risk of vascular disorders in parents and grandparents but not in all relatives. Multivariate analysis indicated family history of stroke as most common only in boys. In conclusion, our study provides some clues to the assumption that migraine and vascular disorders have common pathogenic mechanisms and that genetic susceptibility plays a role in increasing the risk of migraine in the offspring of families with one or more cerebrovascular or cardiovascular conditions.